The Clinical Impact of the Dendritic Cell-based Cancer Vaccine: the Role in the Inflammatory Tumor Micro-environment

Abstract

As a novel therapeutic module, the dendritic cell (DC) based cancer vaccine has been recognized with great hope in eliminating cancers, including minimal residual cells, without harming normal tissue. A key factor in initiating and operating the immune system against foreign bodies including tumor cells, the DC has been regarded as the next possible breakthrough in new cancer therapy. However, the results of more than 15 years of clinical studies with DC vaccine revealed the difficulties fulfilling this expectation. Evidence has disclosed that the DC activation required for proper tumor-specific effector CD4 + and CD8 + T cell stimulation is inhibited in the micro-environment of cancer. Studies have further reported that DC phenotypes in cancer tissue and draining lymph nodes are mostly immature, which results in regulatory immune responses. Also, the existence of myeloid derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs) adversely affect both DC function and immune suppression in the cancer-environment. In this review, the impact of an inflammatory micro-environment induced by cancer on the effect of DC-based cancer immunotherapy and the possibility of a clinical efficacy improvement are discussed.